Humidifier Disinfectant Health Center, Asan Medical Center, Seoul, Republic of Korea.
Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Pediatr Pulmonol. 2022 Dec;57(12):3161-3164. doi: 10.1002/ppul.26139. Epub 2022 Oct 4.
Asthma and postinfectious bronchiolitis obliterans (PIBO) are common chronic lung diseases in company with wheezing in children. However, it is not clear what is common and unique mechanisms between the two diseases. Thus, we used proteomic analysis to compare differences in biomarkers between children with asthma and PIBO.
Overall, 30 healthy children without respiratory underlying diseases, 18 children with asthma and 15 with PIBO were included for this study. Sequential window acquisition of all theoretical mass spectra (SWATH)-mass spectrometry (MS) was used to measure proteins in plasma samples. To identify specific pathways of each groups, we used the ingenuity pathway analysis (IPA) software.
We identified and quantified 354 proteins across all 63 samples in the SWATH-MS analysis. Forty eight proteins were significantly different among 3 groups. The upstream analysis of IPA suggested that inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) was the upstream inhibitor of 4 differentially expressed proteins (DEPs) in asthma, while the upstream activator in PIBO subjects. Among 4 DEPs, TGF-β1 in PIBO and periostin in asthma were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, maximal med-expiratory flow, and PC20, respectively.
These findings demonstrate that transforming growth factor β1 and periostin were unique biomarkers of PIBO and asthma in children, respectively. The mechanism regulated by IKBKB may be therapeutically relevant for PIBO and asthma.
哮喘和感染后细支气管炎性闭塞(PIBO)是儿童中常见的伴有喘息的慢性肺部疾病。然而,目前尚不清楚这两种疾病之间存在哪些共同和独特的机制。因此,我们使用蛋白质组学分析比较了哮喘和 PIBO 患儿生物标志物之间的差异。
本研究共纳入 30 名无呼吸系统基础疾病的健康儿童、18 名哮喘患儿和 15 名 PIBO 患儿。采用序贯窗口采集所有理论质谱(SWATH)-质谱(MS)技术测量血浆样本中的蛋白质。为了确定每个组的特定途径,我们使用了 Ingenuity 通路分析(IPA)软件。
我们在 SWATH-MS 分析中鉴定并定量了 63 个样本中的 354 种蛋白质。3 组间有 48 种蛋白质差异显著。IPA 的上游分析表明,核因子κB 激酶亚单位β抑制剂(IKBKB)是哮喘中 4 个差异表达蛋白(DEPs)的上游抑制剂,而在 PIBO 患者中是上游激活剂。在 4 个 DEPs 中,PIBO 中的转化生长因子-β1(TGF-β1)和哮喘中的骨膜蛋白(periostin)与 1 秒用力呼气容积(FEV1)、FEV1/用力肺活量、最大中期呼气流量和 PC20 分别呈负相关。
这些发现表明,转化生长因子-β1 和骨膜蛋白分别是儿童 PIBO 和哮喘的独特生物标志物。IKBKB 调节的机制可能与 PIBO 和哮喘的治疗相关。